Stop Air Leak by Talc or Autologous Blood Patch Therapy (STOP)

A Pilot Randomised Study Comparing the Clinical Efficacy of Stopping Air Leak by Talc Pleurodesis or Autologous Blood Patch Therapy in Secondary Spontaneous Pneumothorax

Objectives: To compare the therapeutic efficacy and safety profiles of intrapleural talc pleurodesis versus autologous blood patch therapy(ABPT) in patients with secondary spontaneous pneumothorax(SSP) complicated by persistent air leak(PAL), and to assess the trial feasibility for a subsequent full-scale, multicentre randomised controlled trial(RCT).

Hypothesis: Talc pleurodesis and ABPT demonstrate comparable efficacy in stopping PAL and facilitating chest drain removal within 5 days.

Design and subjects: This single-centre, two-arm, open-label pilot RCT will recruit 30 patients with SSP and PAL persisting ≥5 days. Eligible patients will be randomised in a 1:1 ratio to receive intrapleural talc pleurodesis or ABPT. Digital chest drain systems will continuously record air leak rates from 24 hours before randomization until 120 hours post-intervention, ensuring objective, real-time data capture. Patients will be followed till 90 days post-discharge.

Interventions: Recruited subjects with PAL ≥5 days will be randomized in 1:1 ratio to receive talc pleurodesis or ABPT.

Main outcome measures: The primary outcome is complete cessation of air leak and successful chest drain removal within 5 days after the intervention. Secondary outcomes include absolute and percentage changes in digitally measured air leak rates, duration of chest drainage, recurrence of ipsilateral pneumothorax, need for additional pleural interventions, and safety outcomes such as drain blockage and pleural infection.

Data analysis and expected results: Data will be analysed on an intention-to-treat basis for all randomised subjects with regression models adjusting for confounders. The pilot outcomes will inform sample size calculations and refine design parameters for the proposed full-scale multicentre RCT.

Study Overview

• Status: Not yet recruiting
• Conditions: Pneumothorax Spontaneous Secondary
• Intervention / Treatment: Drug: talc powder; Biological: patient's own venous blood

Detailed Description

Pneumothorax, defined as the presence of air in the pleural space, is a common respiratory emergency that often necessitates prolonged hospitalisation. In cases where pneumothorax occurs in the setting of underlying chronic lung diseases (secondary spontaneous pneumothorax, SSP), the clinical course is considerably more severe. SSP patients are typically more hypoxic, more likely to develop persistent air leak (PAL) (exceeding 5-7 days), and experience longer hospital stays with higher in-patient mortality compared to those with primary spontaneous pneumothorax (PSP).

The management of SSP with PAL remains controversial despite its clinical significance. Numerous strategies, including chemical pleurodesis, autologous blood patch therapy (ABPT), implantation of endobronchial valves (EBV), and surgical pleurodesis, are employed in practice. However, many SSP patients are unsuitable for invasive procedures such as EBV placement or surgery, owing to their poor premorbid status. In this context, ABPT and chemical pleurodesis (often using talc) emerge as low-cost, bedside alternatives. Yet, current practices vary widely, and a lack of robust comparative evidence has left clinicians with no definitive guidance regarding the optimal management approach.

Talc pleurodesis, involving the intrapleural instillation of sterile talc powder, is a commonly adopted treatment for SSP with PAL. Retrospective studies indicate that 37.2% to 44.5% of SSP patients undergo chemical pleurodesis, with talc being the predominant agent. Reported treatment success is around 70%, with a median drainage duration of 12 days post-procedure. Adverse events, most notably chest pain affecting roughly one-third of patients, are not uncommon, although more serious complications such as respiratory distress occur in only 1.6% of cases. Nonetheless, these findings are derived from studies with retrospective designs and variable methodologies, limiting firm conclusions on efficacy and safety.

In contrast, ABPT has been proposed as a promising alternative for managing PAL. This technique involves the intrapleural instillation of autologous blood with the aim of sealing the air leak, initially developed for PAL in post-operative pneumothorax. Several small-scale retrospective and prospective studies have suggested that ABPT can achieve cessation in 26% to 91% of cases, with some reports showing 71.7% to 84.0% of patients experiencing complete resolution within five days. Moreover, ABPT appears safe for repeated administration, with adverse events reported at incidences ranging from 0% to 16%. However, the heterogeneous outcomes likely reflect differences in blood dosage, timing of intervention, number of administrations, and varying definitions of PAL among studies.

Given the controversy and the limitations of existing evidence, a multicentre randomised controlled trial (RCT) comparing talc pleurodesis with ABPT is imperative. To achieve this, a pilot study is designed to rigorously address methodological weaknesses by standardising the timing of pleural interventions, employing a digital chest drain system for precise, quantitative measurement of air leak, and adopting unified criteria for treatment success.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Ka Pang Chan, MBChB; Phone Number: +852 3505 2211; Email: chankapang@cuhk.edu.hk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18 years or older
• Radiographically proven pneumothorax and underlying lung disease (either pre-existing or shown in diagnostic imaging at presentation)
• Spontaneous onset of pneumothorax, not related to trauma or iatrogenic procedure
• SSP with air leak persists for ≥3 days after the first radiographic evidence of pneumothorax
• Intend to administer talc or autologous blood patch therapy (ABPT) to stop the air leak as the next step of treatment

Exclusion Criteria:

• A chest drain size smaller than Fr 12
• Bilateral pneumothorax
• Impaired blood clotting, including baseline INR > 1.5, platelet < 150 x 10^9/L, use of therapeutic dose anticoagulant or dual-antiplatelet agents
• Active or recent (within 6 weeks) pleural infection
• Septicaemia or active extrapleural infection (e.g. pneumonia)
• Use of long-term systemic corticosteroids or immunosuppressant
• Previously received talc or ABPT to the ipsilateral pleural space for the current episode of pneumothorax
• Known sensitivity to talc
• Has had a previous pneumonectomy (either on the same or contralateral side)
• Patients who are pregnant or lactating (females of childbearing potential must have a negative pregnancy test before randomisation)
• Expected survival of less than three months from a different pathology to this pneumothorax (e.g. metastatic malignancy)
• Cognitively impaired and physically unable to follow the turning procedure during intrapleural procedure, or at risk of self-removing chest drain
• Inability to give informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: talc pleurodesis; intrapleural instillation of talc slurry	Drug: talc powder; intrapleural instillation of talc slurry
Active Comparator: Autolougs blood patch therapy (ABPT); intrapleural instillation of patient's venous blood	Biological: patient's own venous blood; intrapleural instillation of patient's own venous blood

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete cessation of air leak within 5 days of study intervention	Complete cessation of air leak for more than 24 hours and successful chest drain removal within 5 days after talc pleurodesis or ABPT	5 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the average rate of air leak	Absolute reduction and percentage change in the average rate of air leak (in mL/min) from randomisation to 5 days after the study interventions	5 days
Time to air leak cessation	Time from study intervention to complete cessation of air leak and successful removal of all chest drain(s) (in hours)	30 days
Length of hospital stay	Length of hospital stay after study intervention (in days)	3 months
Recurrence of pneumothorax	Recurrence of ipsilateral pneumothorax after study intervention	3 months
Number of patients requiring additional intervention	The need for additional (unplanned or elective) interventions for persistent air leak, which includes needle aspiration, chest drain insertion, implantation of endobronchial valve, surgery	3 months
Pain score	Pain score in visual analogue scale, score ranges from 0 to 10, with 0 means no pain, and 10 means the worst pain ever	5 days
Breathlessness score	Breathlessness by visual analogue scale, score ranges from 0 to 100, with 0 means no breathlessness, and 100 means the worst breathlessness ever	5 days
Adverse events	Occurrence of adverse events directly related to study interventions (e.g. drain blockage, pleural infection / empyema, fever, acute respiratory distress syndrome)	3 months
Spirometry parameter	Pre-bronchodilater spirometry parameters (forced expiratory volume in 1 second and forced vital capacity, both in liter) at 1 and 3 month follow up	3 months
6-minute walking distance	6-minute walking distance (in meter) at 1 and 3 month follow up	3 months

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong
• Investigators: Study Director: David SC Hui, MD, Chinese University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): March 31, 2029
• Study Completion (Estimated): March 31, 2029

Study Registration Dates

• First Submitted: March 8, 2025
• First Submitted That Met QC Criteria: March 12, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 12, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: talc pleurodesis; Persistent air leak; autologous blood patch therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Respiratory Tract Diseases; Neoplastic Processes; Pleural Diseases; Neoplasm Metastasis; Pneumothorax
• Other Study ID Numbers: STOP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No